Project Summary/Abstract Bariatric surgery is currently the most effective treatment strategy for weight loss in the severely obese. Long-term data on the `gold standard' bariatric operation, Roux-en-Y Gastric Bypass (RYGB), indicate both durable weight loss and a high rate of remission of diabetes after surgery. Recently, Vertical Sleeve Gastrectomy (VSG) has emerged as the most frequently performed bariatric procedure in the U.S. Despite its common use, patients and physicians do not have sufficient, high-quality comparative effectiveness data for VSG to adequately inform treatment decisions between VSG and the gold standard RYGB. Large-scale comparative effectiveness studies, using real-world clinical populations, are urgently needed to fully understand and improve these decisions. We have designed such a study to compare the effectiveness of VSG and RYGB for surgical safety and hypertension, dyslipidemia, and diabetes remission as well as overall CVD risk reduction in 16,693 VSG and 9,943 RYGB patients. This sample size is over 6 times that of VSG patients and over twice the RYGB patients in all published studies directly comparing the effectiveness of VSG and RYGB. No other studies in the published literature have the diversity of bariatric surgery patients that our sample has; 55% are Hispanic or non-Hispanic Black. We will apply innovative econometric techniques to address confounding in observational data and study heterogeneity of treatment effects to inform clinical knowledge and identify areas where further randomized studies are needed. We have assembled an experienced, interdisciplinary econometric, health services, and clinical research team to address the following specific aims over a median three years of follow-up: Aim 1. Compare the effectiveness of VSG and RYGB in remission of CVD risk factors and reduction in overall CVD risk using advanced statistical and econometric techniques; Aim 2. Compare VSG and RYGB surgical safety using similar methods to Aim 1; Aim 3. Understand the treatment effect heterogeneity in remission of CVD risk factors, reduction in overall CVD risk, and safety outcomes for patients with different racial/ethnic backgrounds, sexes, and disease burdens at the time of surgery. With the accomplishment of these aims, we will be able to provide population-based, comprehensive, rigorous evidence for clinical and policy decision-making regarding the choice between RYGB and VSG for overall CVD risk reduction, risk factor remission, and safety.